Journal of Psychosocial Nursing and Mental Health Services

Psychopharmacology 

Pharmacotherapy With Attention-Deficit Disorder

Barbara J. Limandri, PhD, PMHNP, BC

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed mental disorder in children and a small proportion retain the disorder into adulthood. The primary feature of ADHD is inattentiveness that contributes to restlessness, and it is considered a neurodevelopmental disorder characterized by a 2- to 3-year delay in cortical maturation in children. Neurophysiological studies identify functional connectivity changes in the dorsolateral prefrontal cortex, insula, and anterior cingulate cortex. The sympathomimetics that act as dopamine agonists are the mainstay in pharmacological treatment. The current article addresses the definition and manifestations of attention-deficit disorder, comorbidities in children and adults, epidemiology, neurophysiology, and pharmacological treatment strategies. [Journal of Psychosocial Nursing and Mental Health Services, 58(5), 7–14.]

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed mental disorder in children and a small proportion retain the disorder into adulthood. The primary feature of ADHD is inattentiveness that contributes to restlessness, and it is considered a neurodevelopmental disorder characterized by a 2- to 3-year delay in cortical maturation in children. Neurophysiological studies identify functional connectivity changes in the dorsolateral prefrontal cortex, insula, and anterior cingulate cortex. The sympathomimetics that act as dopamine agonists are the mainstay in pharmacological treatment. The current article addresses the definition and manifestations of attention-deficit disorder, comorbidities in children and adults, epidemiology, neurophysiology, and pharmacological treatment strategies. [Journal of Psychosocial Nursing and Mental Health Services, 58(5), 7–14.]

Exploring psychotherapeutic issues and agents in clinical practice

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) identifies attention-deficit/hyperactivity disorder (ADHD) as a neurodevelopmental disorder defined as “a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development” (American Psychiatric Association [APA], 2013, p. 59). Diagnostic criteria include the following: symptoms must be present prior to age 12; symptoms must be present in two or more settings; and there is clear evidence that the symptoms interfere with social, academic, or occupational functioning.

When initial diagnosis is made in adulthood, it is important to obtain collateral information regarding childhood behavior and not rely solely on self-report of the client (APA, 2013). Hyper-activity may not be an accurate descriptor because it implies increased motoric energy, where the increased movement is highly associated with difficulty remaining focused with resultant restlessness. This type of energy is not to be confused with the increased energy associated with mania or cyclothymic disorders (Ghaemi, 2019). Therefore, the term “attention-deficit disorder” (ADD) will be used throughout this article.

It is important to recognize that inattentiveness is not necessarily a disorder but an ordinary cognitive skill in complex environments. Instead, the elements of difficulty remaining focused on a task, poor planning and time-management, and impulsivity contribute to problems in functioning and social relationships. The impairment can be mild, moderate, or severe. Even mild ADD in school-aged children can cause anxiety, poor self-esteem, and interfere with peer relationships (Carbray, 2018).

Epidemiological surveys indicate that ADD occurs in 5% to 11% of children and 2.5% to 4.4% of adults (APA, 2013; Oehrlein et al., 2016). Symptoms present as early as age 4, although it may be difficult to distinguish between normal developmental variation in behavior. When the child enters school, symptoms are more likely to be recognized by teachers and brought to the attention of parents. Symptoms commonly abate as the child's neurological development catches up, and 40% to 60% do not meet criteria for ADD beyond age 25 (Volkow & Swanson, 2013); however, for many individuals the symptoms persist into adulthood. Adult symptoms and functional impairment changes include less hyperactivity and more inattentiveness, impulsivity, and difficulty completing tasks and keeping appointments. Without parental structure, the adult may experience employment and financial difficulties, un- or underemployment, interpersonal problems, and comorbid mental disorders. Major depressive, anxiety, bipolar, and substance use disorders commonly co-occur with ADD, including nicotine use (Volkow & Swanson, 2013). Children with mild and moderate ADD who have been treated behaviorally and pharmacologically often develop compensatory and adaptive strategies to minimize symptomatology in adulthood.

Assessment of Attention-Deficit Disorder

Arriving at a diagnosis of ADD requires the customary assessment strategies of a clinical interview that is broad enough in scope to rule in and rule out different disorders. ADD symptoms can overlap with other diagnoses, such as major depressive, bipolar, anxiety, and substance use disorders. The diagnosis of ADD should not be made in the presence of psychotic symptoms. The standard of practice is to use specific criteria in the DSM-5 to formulate the diagnosis. Because ADD has behavioral and cognitive components, the clinician must use additional observational and data gathering strategies to assure a valid diagnosis before formulating a treatment plan. The standard for children and adults is to gather data with the client's consent from collateral sources (e.g., teachers, family members, coworkers) as well as the client to appraise symptomatology in more than two settings. Documents such as school performance reports, work evaluations, and appointment calendars serve to support assessments. Soliciting information from multiple sources enriches the validity and scope of data to clarify the diagnosis and plan of care.

Between 1999 and 2010 the rate of adults diagnosed with ADD more than doubled and prescriptions for stimulants increased by approximately 700% (Lovett & Davis, 2017; Oehrlein et al., 2016; Olfson et al., 2013). What accounts for this change? In 2004, the U.S. Food and Drug Administration (FDA) approved prescribing mixed salts of amphetamine and methylphenidate for adults, and in 2012, approved the non-stimulant atomoxetine for treatment of adults with ADD.

There are also intrinsic factors that motivate teens and adults to endorse symptoms of ADD. The most obvious is to have legal access to stimulant medications. The main effects of stimulants are enhanced alertness, focus, and energy, which all users (i.e., those with or without ADD) experience when taking these medications. It is not surprising then that high school– and college-aged individuals will seek these effects. Similarly, the diagnosis of ADD may afford the person disability accommodations in school and work. These benefits can consciously and unconsciously influence the client to seek a diagnosis of ADD as a way to explain perceived deficits in abilities and achieve a valid means of compensating. Mental health nurses and other providers likewise may have bias toward making or avoiding the diagnosis and prescribing stimulant medications, thereby adding to the challenge of diagnosing and treating ADD.

In making the diagnosis of ADD in children and especially adults the clinician uses multiple sources of information, including standardized measurement scales (Table 1), the DSM-5 clinician interview schedule (APA, 2013), and collateral informants. Because the relationship between the client and evaluator affects the accuracy of the data, it is advisable to have an external evaluator, such as a psycho-metric psychologist, conduct the interview, especially if the client has a preexisting established relationship with the clinician (Molina & Sibley, 2014). When an advance practice psychiatric nurse is assessing the client, it is important to ask the client what his/her goal is in having the evaluation (e.g., for medication, disability application) (Lovett & Davis, 2017).

Standardized Measurement Tools for Attention-deficit Disorder (ADD)/ADHDStandardized Measurement Tools for Attention-deficit Disorder (ADD)/ADHD

Table 1:

Standardized Measurement Tools for Attention-deficit Disorder (ADD)/ADHD

Neurophysiological Correlates

ADD is a neurodevelopmental disorder with “inefficient tuning of the prefrontal cortex” (Stahl, 2013, p. 475). Neuroimaging studies identify functional connectivity problems between key circuits, primarily with the dopamine and norepinephrine pathways that connect the dorsolateral prefrontal cortex, dorsal anterior cingulate, prefrontal motor cortex, orbitofrontal cortex, and basal ganglia with thinning of the cortices (Gonen-Yaacovi et al., 2016). Dysfunction in the dopamine pathways results in symptoms affecting attention, executive function, impulsivity, motivation, and reward (Volkow & Swanson, 2013). With ADD, these areas of the brain are especially slower to develop in children and may be significantly delayed through early adulthood (Stahl, 2013).

Positive emission tomography studies in individuals with ADD show a decrease in binding of D2/D3 receptors in subcortical areas, including the striatum and midbrain, that contribute to impulsivity and poor tolerance for frustration (Giedd, 2019; Minzenberg, 2012). The dopamine transfer deficit theory (Tripp & Wickens, 2008) explains the neurological role in ADD symptoms. Learning and behavioral response to the environment occurs in response to a stimulus that is positively reinforced; response to stimuli is based on the strength of synaptic connection and dopamine concentration. The striatum, which is rich in dopamine neurons, is crucial in reward-related learning and undergoes considerable neural plasticity (i.e., the ability of neural tissue to reflexively modify and change). Dopamine firing in the substantia nigra and ventral tegmental area results in the ability to predict reinforcers. Activation of the dorsal striatum occurs in relation to reinforcement of action; activation of the nucleus accumbens occurs in relation to reward anticipation. Plasticity follows the three-factor rule: presynaptic activity in cortical inputs to the striatum, post synaptic striatal cell activity, and pulsatile release of dopamine. When there is a delay between stimulus response and reinforcement, there is a decrease in learning.

As the brain develops in childhood, neural growth bridges the gap in delay through dopamine transfer to learn to predict and even anticipate reinforcement. In ADD, that transfer of dopa-mine cell response fails to develop or develops more slowly and anticipation of reinforcement is weak or does not develop at all. With delayed or discontinuous reinforcement, the child does not respond to discipline or correction. As development continues into adolescence and adulthood, the individual demonstrates heightened sensitivity to criticism (Tripp & Wickens, 2008). The reward center is key to the symptomatology of ADD. ADD can be described as an alteration in processing reinforcement, especially in response to learning and predicting reinforcement and tolerating frustration with delayed gratification.

Recognizing the role of dopamine and its metabolite, norepinephrine, in the circuitry between the limbic area of the brain through the cingulate and to the prefrontal cortex in the process of learning to respond to the environment helps consider treatment strategies when the circuitry is faulty. In ADD, there is altered sensitivity to reinforcement due to disrupted dopamine release. As the brain develops, that disrupted circuitry improves, resulting in improvement and change in symptoms from childhood to adolescence and adulthood. Treatment strategies focus on strengthening the dopamine connection by increasing dopamine concentration and release in the circuit between the basal ganglia, striatum, and dorsolateral prefrontal cortex.

Pharmacological Treatment

Given the role of dopamine and norepinephrine in attention to conditioned responses to the environment, learning, and cognitive organization, it is not surprising that dopamine and norepinephrine agonists or reuptake inhibitors provide effective reduction in symptoms. This class of medications is frequently called stimulants; however, the more accurate classification would be dopamine modulators, as dopamine and norepinephrine agonists ultimately regulate the release of dopamine in the striatal-prefrontal cortex circuit.

As early as the 1930s, amphetamines were seen to have a calming effect on boys with ADHD symptoms and this was attributed to a paradoxical effect. With more refined and specific neuroimaging, it is apparent that it is not a paradoxical effect but rather that improved focusing reduces the anxiety accompanying frustration and the child is better able to self-regulate (Hodgkins et al., 2012). Amphetamine salts were first used intentionally to treat the symptoms, and improved formulations of mixing d- and l-amphetamine salts extended the duration of effect for better efficacy and adherence. The major difference in the amphetamine formulations is half-life, and therefore, duration of effectiveness and frequency of dosing. Methylphenidate became an alternative with a similar mechanism of action and pharmacokinetic profile (Schrantee et al., 2018). Other norepinephrine-dopamine reuptake inhibitors and adrenergic agonists were used off-label and have since attained FDA approval for treating ADD in adults and/or children. The one exception is guanfacine, which is not approved for adult ADD due to potential cardiovascular risks (Martinez-Raga et al., 2013).

Table 2 shows the variety of commercially available FDA–approved drugs for ADD. Dosing needs to be individualized to the patient's weight, symptoms, and life circumstances. All medications for children and adults need to be titrated to adequately resolve symptoms within a reasonable quality of daily life. Frequent dosing may pose difficulties for children who are unable or do not want to take repeated doses throughout the day while in school and may need a long-acting medication for school hours and an additional late afternoon short-acting dose to complete homework and after school activities. Similarly, the formulation needs to accommodate the patient's needs and preferences, including a chewable tablet or oral dissolving tablet for children who have difficulty swallowing tablets or a transdermal patch for those who are averse to taking pills. Adults may need more than once per day dosing to meet demands of work but not interfere with sleep (Zhou et al., 2018).

Medications for Attention-Deficit DisorderMedications for Attention-Deficit Disorder

Table 2:

Medications for Attention-Deficit Disorder

When dopamine agonists are used, long-acting formulations tend to improve consistency in symptom control as well as adherence. There is less sleep disturbance when used as monotherapy and diversion is less likely. Studies with lisdexamfetamine indicate greater adherence, especially in teens and adults with similar side effects as shorter-acting medications (Christensen et al., 2010; Coghill et al., 2014; Najib et al., 2017).

Side effects of the dopamine-norepinephrine reuptake inhibitors are similar across formulations. Most common are anorexia, insomnia, headache, weight loss, emotional lability, anxiety, and abdominal pain (Stahl, 2013). These side effects vary for individual patients and can be ameliorated by lowering the dosage, distributing the dose over more frequent times at lower doses, or changing to a different formulation. In children, weight needs to be monitored carefully to assure normal growth patterns. More troublesome side effects include tachycardia and hypertension; therefore, vital signs are important to monitor regularly (Martinez-Raga et al., 2013). Studies have found no long-term effects on the brain except in a dynamic positive effect on the dopamine system (Schrantee et al., 2018; Schweren et al., 2015; Yang et al., 2016).

Treatment of ADD in children and adults must also include nonpharmacological interventions that target organizational and time-management, interpersonal effectiveness, and coping skills. Personal and technological coaching are effective, especially with teens and adults, in building skill and self-efficacy. There are a number of effective smartphone applications (apps) that are inexpensive for teens and adults to use for staying on task. It is also crucial to screen for comorbid conditions including anxiety, depression, and substance use, as these conditions exacerbate ADD and add to the burden of illness (Carbray, 2018; Leahy, 2018).

Non-Medical Use of Stimulants

A frequently expressed concern in prescribing stimulants is possible dependence and addiction to other drugs. More commonly those without ADD seek these medications for non-medical use and to achieve heightened focus and energy and to some extent euphoria. The prevalence of non-medical use of stimulants is higher than illicit use of opioids, sedatives, and benzodiazepines (Liu et al., 2019) In a U.S. national household survey conducted in 2015–2016, 6.6% of adults used prescription stimulants, with 4.5% using without misuse, 1.9% misusing without a use disorder, and 0.2% with use disorders (Compton et al., 2018). Most individuals obtained the medications through friends and family members. Parents of children with ADD have diverted their child's medication for personal use and frequently were identified as also having ADD (Pham et al., 2017). In addition, adolescents have diverted their own prescriptions to classmates and friends (Holt et al., 2018; McCabe et al., 2017).

Methamphetamine should not be confused with amphetamine drugs used to treat ADD. Although they have similar effects on wakefulness, attention, and energy, methamphetamine is a double methylated compound that is much more potent, faster acting, and has a longer duration of action that contributes to dependency. Withdrawal from methamphetamine is more pronounced and can result in fatigue, agitation, depression, psychosis, anxiety, and suicidal ideation and behaviors (Kish, 2008; Mihan et al., 2018). In fact, chronic methamphetamine users have a high incidence of ADD, suggesting screening and treating for ADD when the person is in full recovery may help maintain recovery (Obermeit et al., 2013).

Summary and Clinical Recommendations

ADD is a neurodevelopmental disorder that affects children and contributes to a poorer quality of life if left untreated, potentially leading to chronic low self-esteem, anxiety, difficulty in interpersonal relationship, and academic impediments. With treatment, however, many symptoms abate as the child's brain matures, albeit at a slower pace than children without ADD. A small percentage of adults maintain the symptoms with less hyperactivity but continued inattentiveness, restlessness, irritability, and impulsivity. Adults tend to underachieve, have interpersonal conflicts and partnership strain, mismanage their finances, and have difficulty maintaining a steady job (Coghill et al., 2017). Some argue that adult ADD is significantly underdiagnosed (Maruta et al., 2017; Volkow & Swanson, 2013), whereas others note an implausible rising trend of diagnosis specific to the United States (Oehrlein et al., 2016; Olfson et al., 2013).

Screening for ADD in children is essential in providing early intervention and reducing negative outcomes, as well as thorough assessment of young adults to arrive at an effective treatment plan. The sympathomimetics are the first line of pharmacological treatment and require thoughtful and collaborative dosing and monitoring for effectiveness. In adolescents and adults, treatment also necessitates monitoring for comorbid conditions including substance use. Because clinician bias can covertly affect practice, it is important for psychiatric–mental health nurses to reflect on their own attitudes and beliefs in working with adults with ADD.

Some recommendations for psychiatric–mental health nurse generalists and advance practice nurses include:

  • Use multiple informant sources in assessing for ADD, including persons who interact with the client in different settings and documents that demonstrate behavioral and cognitive symptoms.
  • Use valid and reliable measurement tools along with self-report and interview schedules.
  • Incorporate the DSM-5 online assessment measures in assessments (access https://www.psychiatry.org/psychiatrists/practice/dsm/educational-resources/assessment-measures)
  • When prescribing medications for ADD in adolescents and adults, consider random urine drug screens to assure medication adherence and detect possible other drug use.
  • Routinely review the state Prescription Drug Monitoring Program with each medication refill.
  • Monitor vital signs, especially pulse and blood pressure, when prescribing sympathomimetics.
  • Consider long-acting medications whenever possible to provide consistency of symptom relief.
  • In addition to pharmacotherapy, psychotherapy with a focus on skill building is essential in helping clients achieve self-efficacy in managing their ADD.

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Standardized Measurement Tools for Attention-deficit Disorder (ADD)/ADHD

Instrument/DescriptionAge (y)AdministrationScoringComments
ADHD Rating Scale IV (ADHD-RS-IV) 18 items, subscales correspond to DSM-IV criteria5 to 18Self-report semi-structured parent and teacher forms4-point frequency scale, with higher scores indicating greater frequency of symptomsCan be used as a screening or assessment tool; reliable and easy to administer; demonstrated validity, specificity, and sensitivity
ADHD Rating Scale V (ADHD-RS-V) Two subscales of nine items each to correspond to DSM-5criteria, with additional functional impairment assessment5 to 17Parent and teacher forms4-point frequency scale, with higher scores indicating greater frequency of symptomsAge-appropriate descriptors for children and adolescents; functional impairment items linked to inattentive and impulsive symptoms; demonstrated validity, reliability, specificity and sensitivity
Child Behavior Checklist (CBCL) 120 items in two sections: behavior and performance, social and emotional traits.6 to 18Self-report child, parent, and teacher versionsMixture of free text, yes/no, 3-point Likert scalesWell-validated
Conners Rating Scales 3rd edition6 to 18Parent, teacher, and child self-report4-point frequency scale, with higher scores indicating greater frequency of symptoms.Well-established reliability and validity; easy to administer and score; assesses ADHD symptoms as well as executive functioning, defiance/aggression, peer/family relations
ADHD Rating Scale IV (ADHD-RS-IV) Adult prompts, 18 items, subscales correspond to DSM-IV criteria≥18Self-report completed by patient4-point frequency scale, with higher scores indicating greater frequency of symptoms.Separate impulsivity and inattention subscalesCan be used as a screening or assessment tool; psychometric properties not well established; lack of normative data
Brown ADD Symptom Assessment Scale for Adults (BADDS-Adult) 40 items of five symptom clusters≥18Self-report or clinician interview4-point frequency scale, with higher scores indicating greater frequency of symptoms.Limited validity, specificity, sensitivity data available; moderate correlations with Conners Rating Scales
Conners Adult ADHD Rating Scales (CAARS) 66 items with nine subscales corresponding to DSM-IV criteria≥18Self-report or clinician interview4-point frequency scale, with higher scores indicating greater frequencyEasy to administer; large normative database; specific to adult ADHD symptoms; caution with inaccurate self-report
Diagnostic Interview for ADHD in Adults (DIVA) Interview guide for 18 symptom clusters corresponding to DSM-IVcriteria with concrete examples of current and retrospective behaviors from child to adulthoodAdultsClinician interviewBased on criterion A, B, C, D, E Requires collateral information from partners and family membersHigh discrimination between patients with and without ADHD; takes ∼1.5 hours to complete

Medications for Attention-Deficit Disorder

Drug/FormulationHalf-Life/Duration (h)Daily Dosage (mg)a
Amphetamines
  Amphetamine sulfate
    Dyanavel XR®8 to 122.5 to 20
    Evekeo®62.5 to 60
    Adzenys ER®/XR-ODT®9 to 146.3 to 18.8
  Dextroamphetamine
    Dexedrine®4 to 65 to 60
    Zenzedi®3 to 42.5 to 40
  Mixed dextroamphetamine and amphetamine salts
    Adderall®4 to 62.5 to 40
    Adderall XR®8 to 1210 to 40
    Mydayis®1212.5 to 25
  Lisdexamfetamine
    Vyvanse®10 to 1210 to 70
  Methylphenidate
    Methylin®3 to 42.5 to 60
    Ritalin®3 to 42.5 to 60
    Ritalin LA®3 to 42.5 to 60
    Concerta®3.618 to 72
    Metadate ER®3.420 to 60
    Metadate CD®6.820 to 60
    Quillivant XR®5.620 to 60
    QuilliChew®5.220 to 60
    Aptensio XR®5.410 to 60
    Jornay PM5.920 to 100
    Daytrana® patch4.510 to 30
    Cotempla XR-ODT®417.3 to 51.8
Norepinephrine reuptake inhibitor
  Atomoxetine
    Strattera®2440 to 100
Alpha agonists
  Quanfacine
    Quanfacine ER®18 to 242 to 6
    Tenex®170.5 to 4
    Intuniv®181 to 4
  Clonidine
    Kapvay IR®6 to 200.1 to 0.4
Dopamine norepinephrine reuptake inhibitors
  Bupropion
    Wellbutrin XL®21150 to 450
    Alplenzin®21174 to 348
Authors

Dr. Limandri is Professor Emerita, Linfield College, School of Nursing, McMinnville, Oregon.

The author has disclosed no potential conflicts of interest, financial or otherwise.

Address correspondence to Barbara J. Limandri, PhD, PMHNP, BC, Professor Emerita, 9136 SW 36th Avenue, Portland, OR 97219; e-mail: limandribj@gmail.com.

10.3928/02793695-20200417-01

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